Upper respiratory infections (URIs) include rhinitis, pharyngitis/tonsillitis and laryngitis, and their complications such as sinusitis and ear infection, and are the leading reported reason for primary care physician office visits in the United States. Over two-hundred different viruses have been isolated for URI patients, the most common virus being the rhinovirus. URI cases may also be caused by bacteria, the most common virus being the Group A streptococcus in streptococcal pharyngitis (“strep throat”).
It is important for primary care physicians to determine whether URI cases are viral or bacterial, because, among other things, a bacterial URI patient can be treated with an antibiotic, whereas an antibiotic is ineffective against a viral URI. One complicating factor is that the physician cannot reliably rely on clinical judgment alone since the signs and symptoms of bacterial and viral URI are similar. Therefore, according to current medical practice, the physician typically sends a swabbed specimen from the patient to a laboratory for culturing over a two or three day waiting period, after which the culture is examined by a specialist for a determination whether the culture is viral or bacterial. Due to this delay, many physicians will also automatically prescribe an antibiotic as an advance precautionary treatment in the event that the URI later proves to be bacterial. The associated extra expense and delay not only has financial and personal cost, but also leads to the overuse of antibiotics, antibiotic resistance, and longer and more severe illnesses and, sometimes, to additional primary care and specialist office visits.
It is known that metabolic growth products from bacteria, as they proliferate, produce unique volatile organic compounds (VOCs), also known as analytes, that are released into the air exhaled by a patient's respiratory system. Different bacteria, even different strains of bacteria, produce distinct profiles of analytes, such as amines, sulfides, and carboxylic acids. For example, according to medical reports, Staphylococcus aureus may produce isovaleric acid, butyric acid and/or ammonia; Pseudomonas aeruginosa may emit dimethylsulfide, 2-aminoacetophenone, and/or dimethylpyrazine; and E. coli may produce acetic acid in a glucose-rich media and/or amines in a protein-rich media. These unique analytes or metabolites produce biomarkers or “signatures” in the patient's exhaled breath that can be recognized by vapor analysis.
Vapor analysis has been used for detecting and differentiating chemically diverse analytes by passing a patient's exhaled breath over a colorimetric sensor array having multiple sensors, each constituting a chemoresponsive soluble dye or an insoluble pigment. Examples of such colorimetric sensor arrays are disclosed in U.S. Pat. No. 6,368,558; U.S. Pat. No. 6,495,102; U.S. Pat. No. 7,261,857; U.S. Patent Publication No. 2008/0050839; and U.S. Patent Publication No. 2010/0166604. One sensor can respond to many analytes, and many sensors can respond to any given analyte. A distinct pattern of color responses produced by the colorimetric sensor array provides a characteristic signature for each analyte, and such color response patterns have been used to diagnose various diseases, such as lung cancer, as disclosed, for example, in U.S. Pat. No. 6,319,724; U.S. Patent Publication No. 2010/0191474; International Publication No. WO 2010/079491; and Mazzone et al., “Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetric sensor array,” Thorax 2007; 62:565-568.
As advantageous as such colorimetric sensor arrays have been in detecting analytes and in diagnosing diseases, such as lung cancer, they have not proven to be altogether satisfactory. In particular, existing colorimetric sensor arrays may not detect some reported bacteria biomarkers, analytes and other disease signatures in exhaled breath, or may not detect some reported bacteria biomarkers, analytes and signatures at medically relevant concentrations, e.g., below 100 parts per billion (ppb), due to the low reactivity of the analytes with the dyes and pigments used in existing colorimetric sensor arrays. Such analytes include, but are not limited to, esters, ketones, alcohols, alkenes, and/or hydrocarbons.
Accordingly, a non-invasive, simple, cost-efficient, accurate, and sensitive at medically relevant concentrations, method of, and apparatus for, rapidly diagnosing upper respiratory bacterial infections, that is capable of providing real-time results in the context of a single visit to a physician's office, are needed. Also needed is an improved colorimetric sensor array that can detect not only upper respiratory bacterial infections, but also bacteria in general, especially bacteria associated with other diseases and medical and/or sanitary conditions, whether or not in exhaled breath.
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The apparatus and method components have been represented where appropriate by conventional symbols in the drawings, showing only those specific details that are pertinent to understanding the embodiments of the present invention so as not to obscure the disclosure with details that will be readily apparent to those of ordinary skill in the art having the benefit of the description herein.